Search PubMed⌕ Search

Biomedical subjects

G H Barrows

Publications and source records attributed to G H Barrows.

36 records · Page 2Linked to original sources

Human liver tumors in relation to steroidal usage.

Since 1973 a number of investigators have reported an association between liver neoplasia and steroid usage. Through referral material we have examined the histology of over 250 cases of hepatic neoplasia, most in patients receiving steroid medications. The majority have been benign, predominantly focal nodular hyperplasia (55%) and hepatocellular adenoma (39%). The average age was 31.4 years; 83% had significant steroid exposure with an average duration of 71 months for focal nodular hyperplasia and 79.6 months for hepatocellular adenoma. The type of estrogenic agent was predominantly mestranol; however, during the period mestranol was the most frequently used synthetic steroid. A distinct clinical entity of life threatening hemorrhage from the lesion occurred in 31% of patients with hepatocellular adenoma and 9% of patients with focal nodular hyperplasia. Recurrence of benign tumors has occurred in some patients who continued using steroids and regression has been observed in patients who had incomplete tumor removal but discontinued steroid medication. Medial and intimal vascular changes have been present in a large number of the benign tumors. The relationship of these vascular changes to oncogenesis is unclear, but similar lesions have been described in the peripheral vasculature associated with steroid administration. A number of hepatocellular carcinomas have also been seen. Of significance is the young age of these patients and lack of abnormal histology in adjacent nonneoplastic liver. A striking number of the malignant hepatocellular tumors have been of the uncommon type described as "eosinophilic hepatocellular carcinoma with lamellar fibrosis." The epidemiology of liver lesions within this series is difficult to assess, since the material has been referred from very diverse locations.

Adenoma↗

Immunochemical detection of fecal occult blood--the fecal smear punch-disc test: a new non-invasive screening test for colorectal cancer.

An immunochemical test for fecal occult blood was developed for use in colon cancer screening. The test employs high titer monospecific antisera to intact human hemoglobin in a radial immunodiffusion assay. Patient smears on specially treated filter paper allow screening procedures similar to those using Hemoccult slides. Minimum detectible hemoglobin was 0.3 mg/gm stool, and no cross reactivity with dietary constituents, drugs, or chemicals occurred. The accession of 150 consecutive cases of colon-rectal carcinoma was accomplished from three community hospitals. In each instance, at least one preoperative fecal specimen was obtained for companion smear testing with immunochemical punch-disc and commercial Hemoccult slides. Twenty-nine percent of the cases were found not to be bleeding by either test. Occult bleeding was detected by Hemoccult in 40% of the cases, and occult bleeding was detected by immunochemical testing in 65% of the cases. A surprising discovery was that rectal lesions had a much lower rate of of positiuity with both tests (Hemoccult-29%, Immunochemical-50%) than other locations. These results suggest that immunochemical screening for occult blood loss will provide a higher rate of detection of colon cancer.

Adenocarcinoma↗

Diversion of duodenal contents: its effect on the production of experimental gastric cancer.

Diversion of duodenal contents after gastroenterostomy and vagotomy did not protect 240 laboratory rats from increased risk of gastric carcinoma. They were divided into three groups of 80: group 1 received 0.9 mg of 3-methylcholanthrene injected submucosally into the gastric antrum; groups 2 and 3 had bilateral truncal vagotomy and gastroenterostomy, with carcinogen injected into the gastric submucosa near the anastomosis; group 3 also had total duodenoenteric diversion. Blind histopathologic examination of surviving rats during necropsy eight months later disclosed that cancer had developed in six of 60 (10%) group 1 rats, in 23 of 71 (33%) group 2 rats, and in seven of 27 (22%) group 3 rats. Compared with group 1, groups 2 and 3 had an increased incidence of gastric cancer but did not differ from one another in this regard.

Adenocarcinoma↗

Comparison of avitene, topical thrombin, and gelfoam as sole hemostatic agent in tuboplasties.

Forty-eight virgin guinea pigs were subjected to bilateral sectioning of the uterine horn and cuff type salpingostomy. Avitene, Topical Thrombin, or Gelfoam was used as the sole hemostatic agent in each of three study groups. Bipolar cauterization was used in a control series. These agents were compared with regard to ease of application, degree of adhesion formation, net surface area, and microscopic evaluation of degree of fibrosis and inflammatory reaction. The results revealed no statistically significant differences among the various methods of hemostasis. Data were evaluated by uni- and multivariate analyses. Several trends in the data were noted: the greatest amount of fibrosis was associated with Topical Thrombin and Avitene, and the greatest inflammatory response was associated with Avitene. These agents show no superiority to currently used cautery methods of obtaining hemostasis.

Animals↗

Nuclear uptake of a 17 beta-estradiol-fluorescein derivative as a marker of estrogen dependence.

17-Fluorescein-labeled estradiol was prepared by linkage of fluorescein-isothiocyanate through a succinamide-ethyl-amine chain to the 17 position of 17 beta-estradiol. This compound, N-fluoresceino-N'[17 beta-(estradiol-hemisuccinamido)-ethyl]-thiourea, displaced tritiated estradiol from purified estrogen-receptor protein and readily crossed intact cellular membranes. In female rats, in-vivo injection was followed by nuclear labeling of endometrium, whereas nuclear labeling of non-target tissue was absent. Temperature-dependent nuclear transfer could be visualized directly by fluorescent microscopy when human estradiol target tissue (mammary and proliferative endometrium) was incubated in vitro with the compound. Temperature-dependent nuclear labeling was not present in human non-target tissue, including skeletal muscle, skin, stomach, colon, appendix, and lung, after in-vitro incubation. Temperature-dependent nuclear labeling with the compound was inhibited by estradiol and mixtures of natural and synthetic estrogens. A significant positive correlation of the presence of nuclear labeling in human mammary cancer was obtained with standard dextran-coated charcoal radioligand assay for estradiol receptor. Unlike radiologand assay and cytochemical assays, nuclear uptake of the fluorescein-labeled estradiol appears to require an intact estradiol-receptor mechanism.

Adult↗

Occurrence of a thermostable antigen of ovarian carcinoma in normal tissues and secretions.

Thermostable antigen (TA) occurs in ovarian carcinoma and in certain specialized tissues. High titers of TA were found in nineteen of twenty endocervical extracts but not in myometrium, endometrium, or exocervix. TA was present in all of sixteen cervical mucus samples. Antibodies to perchloric acid extract of bronchus showed cross-reaticity with TA from ovarian carcinoma and cervix. Immunofluorescence with frozen sections revealed TA to be present in the columnar epithelium of ovarian neoplasms, and endocervical glands, in bronchial seromucous glands and in hepatic bile canaliculi. Immunofluorescence and immunodiffusion were used to test for cancer patient antibodies against TA. All sera tested negative. An immunofluorescence inhibition test for circulating TA also tested negative in sera of ovarian and cervical cancer patients.

Adult↗

Automated data processing and radioassays.

Radioassays include (1) radioimmunoassays, (2) competitive protein-binding assays based on competition for limited antibody or specific binding protein, (3) immunoradiometric assay, based on competition for excess labeled antibody, and (4) radioreceptor assays. Most mathematical models describing the relationship between labeled ligand binding and unlabeled ligand concentration have been based on the law of mass action or the isotope dilution principle. These models provide useful data reduction programs, but are theoretically unfactory because competitive radioassay usually is not based on classical dilution principles, labeled and unlabeled ligand do not have to be identical, antibodies (or receptors) are frequently heterogenous, equilibrium usually is not reached, and there is probably steric and cooperative influence on binding. An alternative, more flexible mathematical model based on the probability or binding collisions being restricted by the surface area of reactive divalent sites on antibody and on univalent antigen has been derived. Application of these models to automated data reduction allows standard curves to be fitted by a mathematical expression, and unknown values are calculated from binding data. The vitrues and pitfalls are presented of point-to-point data reduction, linear transformations, and curvilinear fitting approaches. A third-order polynomial using the square root of concentration closely approximates the mathematical model based on probability, and in our experience this method provides the most acceptable results with all varieties of radioassays. With this curvilinear system, linear point connection should be used between the zero standard and the beginning of significant dose response, and also towards saturation. The importance is stressed of limiting the range of reported automated assay results to that portion of the standard curve that delivers optimal sensitivity. Published methods for automated data reduction of Scatchard plots for radioreceptor assay are limited by calculation of a single mean K value. The quality of the input data is generally the limiting factor in achieving good precision with automated as it is with manual data reduction. The major advantages of computerized curve fitting include: (1) handling large amounts of data rapidly and without computational error; (2) providing useful quality-control data; (3) indicating within-batch variance of the test results; (4) providing ongoing quality-control charts and between assay variance.

Electronic Data Processing↗

Immunochemical detection of human blood in feces.

Current methods for testing stool samples for hemoglobin utilize peroxidase oxidation of chemical indicators such as guaiac or benzidine. These tests have frequent false-positive and false-negative results, complicating random screening for occult gastrointestinal bleeding. The authors have developed an immunochemical test for human blood in feces using goat antibodies to hemoglobin. When employed in radial immunoassay the test is uncomplicated by cross-reaction with common human foods or other nonhemorrhagic fecal fecal constitutents. The lower limit of sensitivity for hemoglobin in stool samples is 10 mg/dl, compared with a commonly reported threshold of 100 mg/dl for peroxidase tests. The test accurately detects hemoglobin in mixtures of human blood and feces. Immunochemical identification of human blood in stool offers improved detection of lower gastrointestinal bleeding.

Animals↗

Liver lesions and oral contraceptive steroids.

Two strains of mice, CF-LP and Swiss-Webster random-bred, were evaluated for liver neoplasia after administration of oral contraceptive steroids. No increased incidence of hepatocellular tumors was found beyond the variation expected by chance. The overall tumor incidence in treated and untreated groups was identical. No significant increase in tumor size was observed in the treated animals. Liver weights progressively increased in several of the treated groups. In both treated and untreated animals hepatocellular neoplasia was usually accompanied by intracytoplasmic inclusions similar to those observed in human liver tumors. Vascular lesions were observed in some of the animals receiving large doses of contraceptive steroids. While these may be the result of local toxicity, their similarity to lesions observed in benign liver tumors warrants further investigation. No evidence was found to suggest that contraceptive steroids act as initiators of liver neoplasia.

Animals↗

Appearance, properties, and origin of altered human hemoglobin in feces.

Altered hemoglobin (Hb) has been found in the feces as a sequel to an upper gastrointestinal bleed. Active Hb antigen of increased anodic mobility was detected on immunoelectrophoresis of melena stools using a goat anti-Hb. The Hb derivative was also identified in polyacrylamide gel electrophoresis using 412 nm. absorbance. The alteration could be simulated in vitro by incubation of hemolysate with duodenal juice or purified carboxypeptidase B alone, or by a mixture of carboxypeptidases A and B. Treatment of hemolysate or purified Hb with acid, gastric juice, pepsin, pancreatic juice, bile, trypsin, or chymotrypsin failed to produce the characteristic alteration. Instead, no change, or production of alpha and beta chains, or gradual but complete elimination of the Hb antigen was seen. This latter all or none pattern is presumed to prevail in the large bowel on the basis of incubations of hemoglobin-feces mixtures. Individuals documented to be bleeding into the colon were found to have at least a portion of their Hb antigen in the unaltered form by immunoelectrophoresis. This finding may be of value in identifying the general origin of a gastrointestinal bleed.

Carboxypeptidases↗

Quenching curves: solutions by second-order polynomial regression.

This paper describes an inexpensive practical approach for the automated computation of quench corrections in beta-scintillation experiments, using a table-top calculator. This approach applies a second-order fit, ax2 + bx + c = y, where x is the channel A/B ratio for known quench standards and y describes efficiency. There is excellent agreement between measured values and the polynomial expression for most experimental A/B ratios.

Electronic Data Processing↗

Liver tumors in women on contraceptive steroids.

The possible association between oral contraceptives and benign liver tumors has recently been reported. To date the majority of cases have been diagnosed as benign hepatomas (liver cell adenomas). We have had the opportunity to study 13 such cases. Eight have been examples of focal nodular hyperplasia of the liver; however, in addition, there were examples of hepatocellular carcinoma, liver cell adenoma, and possible liver cell hamartoma; all were in women on "the pill." Gynecologists are alerted to the fact that many of the patients present with symptoms of acute abdomen, syncope or shock, and intrahepatic or intraperitoneal bleeding. Prompt diagnosis and treatment may be lifesaving.

Abdomen, Acute↗

Pulse labeling of hydroxyproline and leucine in reproductive tissues: a model for assessment of degree of reactivity.

A prospective study evaluating tissue reactivity by light microscopic and pulse labeling-autoradiographic techniques is presented. One uterine horn of a Sprague-Dawley rat model was subjected to transection and reanastomosis using microsurgical techniques (control). The opposite horn of each was also cross-sectioned with the application of an absorbable topical hemostatic agent (Avitene) and then reanastomosed. After closure of the abdomen, the animals were randomly assigned to groups according to the planned day of sacrifice (days 3, 7, 14, 21, or 28). Autoradiographic techniques utilizing [3H]hydroxyproline or [3H]leucine as well as light microscopy were employed to determine tissue reactivity. The results demonstrated an increase in stromal (P less than or equal to .05) and smooth muscle (P less than or equal to .01) reactivity with [3H]leucine labeling, and an increase in smooth muscle (P less than or equal to 0.05) reactivity with [3H]hydroxyproline in the Avitene-treated groups. It is concluded that pulse labeling with tritiated leucine and hydroxyproline is an effective method of objective analysis of tissue reactivity in reproductive organs.

Animals↗

Application of DNA probes to hematology: an overview with selected examples.

Recent advances in molecular genetics have allowed development of short segments of desoxyribonucleic acid (DNA) which are complementary to active genetic sites. By pairing normal DNA with these "molecular probes", the presence of specific genetic sequences may be detected in patient samples. The majority of hematologic diseases arise from hereditary errors, neoplastic change or parasitic organisms. These types of disorders are particularly suited to diagnosis and management using detection of abnormal DNA sequences. Sensitive laboratory techniques employing these molecular probes are now available directly to detect target DNA sequences, assess abnormal short sequences of DNA, and evaluate the presence of abnormal DNA from its transcription products. Using DNA polymerase amplification, the sensitivity of these methods approaches its theoretical limitation of a single gene pair. In hematology, a prevalent application has been the detection of clonal molecular rearrangements which serves as a marker for lymphocytic neoplasia. Other applications of these techniques include the detection of abnormal chromosomal regions such as the Philadelphia chromosome and the detection of deletions of DNA which occur in such diseases as the myeloid dysplastic syndrome. As more human genetic sequences are known, it seems likely that these techniques will become prevalent among methods of laboratory testing.

Biomarkers, Tumor↗